IL27090A - 17-acetyl-13beta-ethyl-gon-4-en-3-one derivatives and process for the manufacture thereof - Google Patents

Description

This invention having progestational or other steroid hormone activity which are intermediates the production of such steroid The invention also relates processes for producing the compounds and to pharmaceutical compositions tainin certain of The steroid compounds of the invention are those havin formula is a carbonyl or ketalised carbonyl and the hydrogen atoms H at positions 9 and 14 and the roup at on ring G are in the iguration and the hydrogen atom H at position 10 is cis o the ethyl and the at position 17 on ring D designates that the side chain is either cis or trans the compounds in which X is a hydroxymethylene or ketalised carbonyl group are intermediates which are oxidised or hydrolysed respectively to compounds in which X is a carbonyl group which have or other steroid hormone Thus has 10 times the progestational activity of progesterone and its isomer has progestational activity and an oral parenteral ratio of using standard test The invention also concerns processes for the production of steroid compounds having the formula in which a steroid compound of formula in which one or both of X and Z are hydroxymethylene any remaining X or Z group which is not such a group being a carbonyl group or in the case of X a ketalised carbonyl the dotted lines signify an ethylenic bond terminating at the the group at position is in either configuration and the configurations at positions d 14 are as defined is oxidised at one or both of the 3 and 20 a steroid compound of formula where X is a hydroxymethylene a carbonyl group a carbonyl group Y is a carbonyl group in conjunction with an ethylenic bond terminating at the or a protected carbonyl group in conjunction with unsaturation in rings A and B indicated by the dotted lines such that it is hydrolysable to a or one or both of X and Y being a protected carbonyl the group at 7 in either configuration and the configurations at positions and are as defined is hydrolysed to remove the protecting group or groups at one or both of the 3 and 20 a steroid compound of formula where the dotted lines signify the presence of an ethylenic bond at the or 5 group at position is in either configuration and the configurationsat position and are as defined is isomerised to shift the ethylenic bond to the or a steroid compound of formula in which Hal is a halogen preferably bromine or chlorine in the a or the and the group at position can be in either configuration and the configuration at positions 13 are as defined is dehydrohalogenated to introduce a when oxidation of a hydroxymethylene group X to a carbonyl reaction of a carbonyl group X with a ketalising hydrolysis of a protected ketalised carbonyl group X or a reduction of a carbonyl group X to a hydroxymethylene group and again where necessary isomerisation of an ethylenic bond at the or to the or of a chain to a The oxidation process is conveniently carried out using a conventional oxidising chromic acid or by the Oppenauer If the double bond in ring A is at the or 5 the oxidation should be carried out under conditions which are sufficiently acidic or basic to isomerise it to the Starting compounds of formula are readily made by standard procedures from known compounds to make a starting compound of formula where Z is a carbonyl group there may be hydrolysed a compound of formula where Z is a protected oxo group which in conjunction with uneaturation in rings A and B indicated by the dotted lines is hydrolysable by acid to a or a Z can be a single substituted or unsubstituted aliphatic hydrocarbon group or acyl group linked to ring A by nitrogen or sulphur in conjunction with two ethylenic one of which terminates at the and the other at the it can also be two substituted or unsubstituted aliphatic hydrocarbon groups can be joined linked to ring A by oxygen or sulphur in conjunction with a single ethylenic bond terminating at the Preferably the organic radical of Z is a wholly carbon Z can be and is preferably alkoxy example methoxy or or it can be a substituted alkoxy group example a or dihydroxy ropyloxy It can be an alkylthio group example ethylthio or an acyloxy group example or a disubstituted amino group example It can also be an alk dioxy group an ethylenedioxy or an or alkylene thiooxy Thus the starting compounds are exemplified by and enamines of the corresponding the thioketals or hemithioketals of or The hydrolysis is normally with acid but where the protecting group is an ester group it can additionally be hydrolysed by base and certain enamines can be hydrolysed under neutral or basic The unsaturation in ring A is such that hydrolysis removes the organic portion of the group Z and converts it and any ethylenic bond terminating at the position to an oxo Under sufficiently acid conditions or under basic conditions the ethylenic bond terminating at the if not already at the is rearranged to that Normally strong acids such as mineral hydrochloric acid or alkalies are used for this A weaker acid such as an organic acid oxalic can be used for the hydrolysis where the double bond is already at the or alternatively a double bond at the or can be isomerised to the during the oxidation step as mentioned Thus for it will be appreciated that mild hydrolysis of a for instance with a weak organic acid such as aqueous alcoholic oxalic acid at will give a which is readily isomerised to a with stronger acid treatment or with a such a 2 stage process is a well known chemical equivalent of the direct 1 stage hydrolysis under more vigorous acid conditions using a strong usually a mineral acid such as hydrochloric as with hydrochloric acid at Moreover a 1 side chain can be equilibrated by acid or base to give a mixture of predominantly together with some The concept of protecting an oxo or carbonyl group as a derivative such as those mentioned above and their removal to regenerate the oxo or carbonyl group is well known Steroid The earlier starting compounds can be prepared from British Patent by known For instance this can be by British Patent followed by conversion of the resulting by treatment with to give a dibromoacetyl group and debromination with zinc and acetic acid to give a for instance as shown in Example Such a compound can be subjected to Birch redustion for instance as shown is Example 1 to give a when there is simultaneous deacetoxylation and reduction at Alternatively deacetoxylation of the intermediate can be effected prior to Birch reduction by treatment with calcium in liquid ammonia to give a intermediate which can be subjected to Birch reduction as such to give a or can be ketalised and then subjected to Birch reduction to give a Alternatively the intermediate can be hydrated with mercuric sulphate to give a intermediate which in turn is hydrogenated to 17 the latter compound can be subjected to Birch reduction as mentioned Again in a further method of preparing the starting materials a is ethylated to give a e which is dehydrated to a intermediate and this is in turn hydrated by the hydroboration to give a as Such an intermediate can be submitted to Birch reduction and hydrolysed with to give a starting compound of formula The hydrolysis as above mentioned of a compound of structure gives a starting compound of structure where Z is a carbonyl group and X is a hydroxymethylene Starting compounds where Z is a group and X is a hydroxymethylene carbonyl or protected carbonyl group can be made by starting with a or or building up the side chain at position described above and then removing any protecting group by Referring now to the hydrolysis process the group Y in formula and its hydrolysis when it is a protected carbonyl group are exemplified in the same way as for the protected oxo group Z in formula The group X when a protected carbonyl group and its hydrolysis are similarly In the starting compounds can be prepared by known methods as by the general procedures outlined Starting compounds where X is a protected carbonyl group can readily be prepared from the corresponding where X is a carbonyl by forming the desired derivative and then converting the ring A end of the molecule to one having a group Y and unsaturation as described As an example a can be ethylated to give a e is dehydrated to a and this in turn is hydrated instance by the to give a latter can be oxidised to a acetyl compound the graup therein protected by being submitted to Birch and the group removed during subsequent hydrolysis with asid in accordance with the The process can be performed with a strong as a mineral acid hydrochloric acid in a suitable solvent such as or aqueous It also be by treatment with a base in a similar If the acidic or basic conditions are sufficiently strong not only is the ring A double but the side chain is epimerised to give a mixture from which both and can be Thus methanolic hydrochloric acid under reflux for causes the appearance of about from the Less vigorous acid conditions substantially avoid this epimerisation and more vigorous acid conditions are preferable if epimerisation is Similarly treatment of the with methanolic potassium hydroxide at for hours gives a mixture containing about of the but with more dilute alkali for a shorter time epimerisation is The compounds can be readily prepared by known methods as indicated For example a by Birch redustion of a corresponding or can be hydrolysed with a mild acid hydrolysing agent such as a weak organic acid in a lower alkanol to give the corresponding The latter may be for instance with chromic acid or by the Oppenauer method or using the acetic sulphoxide method to give the corresponding compound Oppenauer method will tend to epimerise any to the The dehydrohalogenation reaction is conveniently carried out in conventional mannerfor instance in the presence of a weak or insoluble base example a tertiary amine such as pyridine or collidine or an insoluble carbonate such as an or a basic salt as misiteate alkaline earth metal carbonate or lithium or in presence of a halide ion acceptor such as a boron or aluminium halide Dehydrobromination can also be effected by reaction with a carbonyl blocking agent such as a substituted hydrazine semicarbazide or followed by hydrolytic removal of the blocking See also Steroid Chapter The basic conditions used should be mild enough to avoid rearrangemeat of ring A by the Favo sky To prepare a conveniently the product of the process of the invention is epimerised using strongly acid or basic for instance as shown in Example The starting compounds can be readily prepared by catalytic hydrogenation of a to give a The oxo group can then be protected as a derivative group Steroid for instance as a hemithioketal thioketal or by reduction to a which can be converted to a A group if not present is then introduced and a side chain is built up by known methods as described above to give a Alternatively a latter compound can be prepared from norethisterone as shown in Example ethyl The is then halogenated by conventional procedures Djerassi to give the desired starting preferably using a quarternary ammonium or tertiary amine perbromide such as the ammonium trihalide reagent of Marquet et Chi and Using the latter procedures a protected particularly a enol acetate or enol can similarly be In the structural formulae to a continuous line connecting an atom or group to the tetracyclic nucleus has no configurational but is used solely to indicate the position in the nucleus to which the atom or group is Thus in these structures the and compounds are not separately as unless the product has been obtained by a synthesis which has included a resolution stage and for using the terminology of the Convention approved by Fieser and at page resolved having the 8β this and its antipode the with configuration will be present in equimolecular mixture or racemate one enantiomer being or dextrorotatory and the other In the Examples below such structures are designated as in accordance with the aforementioned Position is also an centre and for convenience and brevity in the foregoing passages on the preparation of starting configurations at this position have been referred to as or In such cases this is with reference to the having the without reference to the state of resolution of the compound referred to and an equivalent meaning is that a group designated is cis to the group at position and if designated is trans to that Preferably the starting material in a process of the invention is a resolved The invention particularly includes the having the group in the presence or absence of their it includes the resolved compounds and the forms in admixture with the corresponding especially racemic The also provides a pharmaceutical composition comprising a of formula I as aforementioned and a pharmacologically acceptable The pharmaceutical compositions of the invention can be formulated in liquid or solid for instance as dispersible and the like by combining them with conventional Such conventional carriers include magnesium carbonate or methyl sodium carboxymethyl low melting wax and cocoa flavouring suspending binders or tablet disintegrating agents can be Powders and tablets preferably contain 5 or 10 to of the active The active steroid can be formulated with an encapsulating material with or without other carriersβ Liquid preparations such as suspensions or emulsions can also be Such preparations include dispersions in a pharmaceutically acceptable liquid carrier such as arachis oil or sterile preferably containing a surface active agent such as fatty acid esters of polyhydroxy compounds sorbitan instance polyethylene oxide fatty acid esters such as Tween aqueous starch in sodium carboxymethyl cellulose aqueous propylene glycol Thus a propylene glycol solution can be used for parenteral injection by utilising natural or synthestic methyl cellulose or other suspending The composition can be in unit dose form in which the dose unit is for instance from to 20 of the active depending on the therapeutic use The unit dose form can be a packages composition packeted vials or ampoules or for example in the form of cachets or tablets or any A EXAMPLE 1 7 triene was shaken with acid and acetic anhydride until the solution was homogeneous and then allowed to stand at room temperature for 12 The reaction mixture was decomposed by stirring with water containing a little pyridine and extracted with The ethereal solutio was washed with 2N aqueous sodium dilute hydrochloric brine and dried The solvent was evaporated and the crystalline residue dissolved in benzene and filtered through a short column of The product was recrystallised from acetate to give the title Infrared absorption triene was dissolved in tertiary butanol and water and was The reaction mixture was allowed to stand for 15 then water was added and the mixture cooled to and allowed to stand for 3 The precipitated product was washed with aqueous methanol and dried to give the title in acetic acid water sodium acetate was heated with zinc dust for minutes with The mixture was filtered and the product precipitated from the filtrate by the addition of The mixture was filtered and the residue dried and recrystallised from ethyl acetate methanol to give the title Infrared absorption triene in dioxan was added to a stirred solution of lithium in liquid ammonia After 30 minutes methanol was added followed by lithium in small Addition of water and extraction with ether gave a gum which was refluxed for minutes with 4N hydrochloric acid in methanol Addition of water and extraction with ether gave a gum which was dissolved in acetone containing anhydrous magnesium sulphate and 8N chromic acid was added dropwise with swirling until the solution assumed a permanent Excess isopropanol was added and the solution evaporated almost to Addition of water and extraction with ether gave a gum which crystallised with Filtration through alumina with and recrystallisation of the product from ethyl acetate ether gave Infrared absorption EXAMPLE 2 A solution of in pyridine and phosphorus chloride was refluxed 2 hours then the cooled reaction mixture was cautiously poured onto The mixture was extracted with washed with hydrochloric sodium bicarbonate and The ethereal solution was evaporated and the residue recrystallised from ethanol to give the title compound 9 s A stream of diborane by the gradual addition of sodium borohydride 1 in diethyleneglycol dimethyl ether 00 to boron trifluoride etherate 105 in glycol dimethyl ether was passed through a solution of in dry tetrahydrofuran for 90 The mixture was allowed to stand for 16 hours and then cautiously decomposed by the addition of Sodium hydroxide 15 in water and hydrogen peroxide was added and the mixture refluxed with stirring for 1 The cooled solution was extracted with the ethereal solution washed with dried and evaporated and the residue recrystallised from acetonitrile to give the title compound Further purification gave a 8θ A solution of 1 in tetrahydrofuran was added to distilled liquid ammonia and lithium was added in small The mixture was stirred for 1 hour and then ethanol was added over a period of When the blue colour was most of the ammonia was evaporated and to water and acidified 6 with acetic The mixture was extracted with and the ethereal solution washed with aqueous sodium water and The ethereal solution was evaporated and the residue recrystallised from ethanol to give the title compound go infrared absorption peaks at 1 A mixture of go acid water and methanol was stirred at for 1 The precipitate was filtered and dried to give the title compound ultraviolet absorption peak at 242 infrared absorption peaks at From the mother liquor was obtained more material To a solution of drox in acetone was added 8N chromic acid over 5 minutes at The mixture was stirred at for then excess isopropanol and magnesium sulphate were and the mixture Benzene was added to the which was washed with aqueous sodium dried and The residue was recrystallised from hexane and dried to give the title product infrared absorption peaks at ultraviolet absorption maximum at 241 EXAMPLE 3 5β A solution of in dioxane was added to a solution of calcium liquid ammonia cc and the mixture stirred for a further 30 Ammonium chloride was the ammonia evaporated and water added and the precipitate dried and recrystallised from ethyl to yield the title compound infrared absorption peaks at 5 in methanol was stirred with potassium hydroxide 1 at for hours in an atmosphere of The mixture was diluted with with water and brine and Evaporation of the solvent gave a gum consisting of the title compound contaminated with starting material analysis of proton magnetic resonance spectrum and Reduction of triene equilibrium mixture described in the previous with lithium and ethanol in liquid ammonia followed by acid hydrolysis and chromic acid oxidation as described for 1 gave the title compound containing about of the magnetic resonance absorption of and of the former EXAMPLE 3 and 1 triene in acetone was treated with 8N chromic acid and the mixture allowed to stand at for 30 minutes Excess reagent was decomposed by the addition of and the mixture filtered through The filtrate was evaporated and the resultant gum crystallised from ethanol to give the first title compound Further purification gave a sample infrared absorption peak at This compound can be subjected to Birch hydrolysis with methanolic hydrochloric acid and oxidation with chromic acid in acetone as in Example 2 to give the same product EXAMPLE 5 ketal e 3 see Example in toluene and ethylene glycol was refluxed with acid for 18 hours with continuous removal of water0 Ether was added to the cooled solution which was washed with aqueous sodium brine and The solvent was removed to leave the title compound mixture of and as a having no carbonyl absorption in the The foregoing ethylene ketal in dioxan was added to a stirred solution of lithium in liquid ammonia After 30 methanol was added followed by lithium in small Addition of water and extraction with ether gave ethylene ketal as a gum This was stirred at for 1 hour with 10N hydrochloric acid 1 in methanol and water 1 Addition of water and extraction with ether gave a gum which was graphed on alumina and crystallised from ethyl acetate to give the title compound The infrared absorption and EXAMPLE 6 ethyl 5 10 diene Example was stirred in methanol containing water and oxalic acid dihydrate until the solid dissolved and was kept at room temperature for 1 The product was isolated by extraction with ether and crystallisation from methanol to give the title compound A solution of the foregoing in methanol containing oxalic acid dihydrate was stirred at room temperature for 1 Dilution with washing with saturated aqueous sodium water and stripping in vacuo gave a Recrystallisation methanol containing a drop of pyridine gave the title compound go no UV The foregoing 1 isopropoxide toluene and were refluxed under nitrogen for 3 The product was isolated by adding extraction with ether and evaporation to dryness to give the title compound in admixture with the as a solid as prepared above was refluxed for minutes chloric acid 10 in methanol The product was isolated by addition of extracted with chromatographed through a short column of alumina and crystallised from hexane to give The mother liquor residue was crystallised several times from to give the 6 2 EXAMPLE propane methanol and acid was refluxed for The solution was excess sodium bicarbonate was added and the mixture was poured into ice The product was isolated by extraction with benzene and crystallisation from methanol containing a trace of pyridine to give eth as a crystalline This was subjected to Oppenauer oxidation by the procedure of Example 6 to give after crystallisation from methanol containing a trace of pyridine e 5o86 250 This compound was sitrred at for 1 hour with 10N hydrochloric in methanol and water 1 Addition of ether alumina and crystallisation of the product from ethyl acetate gave 8 Similarly to Example 7 to in a minimum amount of refluxing methanol was added drops of Cooling to room temperature crystallisation of the product followed by Oppenauer oxidation gave This compound was hydrolysed by refluxing in methanol 10 and water containing acetic acid and sodium acetate for hours and then poured into extracted with and crystallised from to give the same ene go dry redistilled dimethylsulphoxide 10 and acetic anhydride were stirred at for The mixture was poured into potassium carbonate extracted with ether and crystallised from methanol containing a little pyridine to give This was treated with methanolic hydrochloric acid as in Example 6 to give EXAMPLE 10 diene Example was stirred in methanol containing water and oxalic acid dihydrate until the solid dissolved and was kept at room temperature for 1 The product was isolated by extraction with ether and crystallisation from methanol to give the title compound go IBs 1 dry redistilled dimethyl sulphoxide and acetic anhydride were stirred at for The mixture was poured into potassium carbonate extracted with ether and crystallised from methanol containing a little pyridine to give the crude title one was stirred at for 1 hour with 10N hydrochloric acid in methanol and water Addition of ether extraction and crystallisation from ethyl gave the title compound 1 EXAMPLE was dissolved in ethanol and added to a solution of sodium in ethanol The mixture was kept at for hour under The product was isolated by extraction with chromatography on alumina and crystallisation from ethyl to give one EXAMPLE 12 in 100 methanolic potassium hydroxide was kept under nitrogen at 2k After acidification and extraction with the product was passed through a short column of eluting with The fractions were evaporated and the residue was crystallised twice from to give The combined mother liquors were evaporated and the residue crystallised twice from to give 2 0 m 16 EXAMPLE hy 3 in ethanol was hydrogenated in the presence of palladium on charcoal until the uptake of hydrogen had ceasedo After filtration of the catalyst and evaporation of the the residue was crystallised from to afford the title ketal The previous title compound in toluene and ethylene glycol was refluxed with acid with continuous removal of Ether extraction then gave the title compound This compound is also prepared by catalytic hydrogenation as above of to give ketalisation as above to give the ethylene oxidation with chromium trioxide in acetone to give the and e on with ethyl ethylene ketal The previous title compound 1 in pyridine and phosphorus oxychloride was refluxed for 2 hours and the cooled reaction mixture poured onto Extraction with ether then gave the derivative which was treated in dry tetrahydrofuran 30 with pure The mixture was allowed to stand for hours and then cautiously decomposed by addition of Sodium hydroxide in water 120 and hydrogen peroxide 12 was added and the mixture was refluxed with stirring for 1 The cooled solution was extracted with ether and the residue crystallised from methanol to give the title and its 3 ketal The foregoing title compound 0 5 and phenyl ammonium tribromide et and 0 in tetrahydrofuran 10 were kept at for 16 hours0 The product was isolated by pouring the reaction mixture into sodium bicarbonate solution and extraction with ether to give the title compound ketal which the parent ketone awas isolated by treatment at for 5 hours in acetone 15 water 0 3 and acid 02 or treatment with N hydrochloric acid in methanol 20 containing water 1 for hours at and crystallisation from methanols The parent ketone was also obtained by similar of the starting compound and bromination in the same The bromination pyridinium reaction proceeds similarly using perbromide in pyridine at for 1 hour with removal of excess of reagent with sodium thiosulphate and isolation of the product by dilution with dilute acid in the to avoid and extraction with 2k The foregoing in acetone solution containing anhydrous magnesium was treated drop ise with 8N chromic acid with swirling until the solution assumed a permanent Excess isopropanol was added and the solution was evaporated water was added and the product was isolated by extraction with e This compound atent of trimethylbenzylammonium misiteate to give dilution with extraction with ether and crystallisation from the title compound go and 241 EXAMPLE 14 g o prepared as above in 100 methanolic potassium hydroxide was kept under nitrogen at for 24 hours After acidification and extraction with benzene the product was passed through a short column of basic eluting with benzene The factions were evaporated and the residue crystallised twice from to The combined mother liquors were evaporated and the residue crystallised twice from to give g o 240 insufficientOCRQuality

Claims (1)

1. CLAIMS A steroid compound of formula (I) where X is a hydroxymethylene, carbonyl or ketalised carbonyl group; and the hydrogen atoms H at positions 8, 9 and 14 and the ethyl group at position -13 on ring G are in' the trans- anti-trans configuration and the hydrogen atom H at position 10 is cis to the ethyl group, and the ) at position 17 on ring D designates that the side chain -X-CH-, is either cis or trans to the 13-ethyl group. 17P-Acetyl-i3p-ethyl-gon- h-3-one. - 17a-Acetyl-13p-eth'yl-gon- -en-3TO.ne. \' · " ' ' .j . . ' ' . ' · . · " ' i id compound of formula .(I) . where X is a hydroxymethylene, carbonyl or ketalised carbonyl group; I and the hydrogen atoms H at positions 8,9 and 1¼ and the ethyl group at position -13 in ring C are in the trans-anti-trans configuration and the hydrogen atom H at position 10 is cis_ to the ethyl group, particularly 17P-acetyl-13(5-ethyl~gon-½-en-3-one, . in whichs (a) a steroid compound of formula (II) X-50-fa in which one or both of X and Z are hydroxymethylene groups, any remaining X or Z group which is not such a group being a carbonyl group or in the case of X a protected, eng ketalised carbonyl group, the dotted lines signify an ethylenic bond terminating at the 5- position, the group at position 17 is in either configuration and the configurations at positions 8,9«13 and l are as defined above, is oxidised at one or both of the 3 and 20 positions5 (b) a steroid compound of formula (III) where X is a hydroxy methylene group, a carbonyl group or a protected, e.g a ketalised carbonyl group, Y is a carbonyl group in conjunction with an ethylenic bond terminating at the 5-position or a protected carbonyl group in conjunction with unsaturation in rings A and B indicated by the dotted lines such that it is hydrolysable to a ^,5- or 5(10)-ethylenic-3-ketone, one or both of X and Y being a protected carbonyl group, the group at positional? is in either configuration and the configurations at positions 8,9»13 and l are as defined above, cleatte is hydrolysed to «ap-pow the protecting group or groups at one or both of the 3 and 20 positions; (c) a steroid compound of formula (IV) (IV) 4- X~50~fa where the dotted lines signify the presence of an ethylenic bond at the 5(10) or 5i6~position, the group at position 17 is in either configuration and the configuration at positions 8,9,13 and Ik are as defined above, is isomerised to shift the ethylenic bond to the „5~positionj or (d) a steroid compound of formula (V) in which Hal is a halogen atom, preferably bromine or chlorine, in the a or β-configuration, the 5-hydrogen atom and the group at position 17 can be in either configuration and the configurations at positions 8,9?13 and Ik are as defined above, is dehydrohalogenated to introduce a bond? With, when necessary, oxidation of a hydroxymethylene group X to a carbonyl group, reaction of a carbonyl group X with a ketalising alcohol, hydrolysis of a protected e»g. ketalised carbonyl group X or reduction of a carbonyl group X to a hydroxy- methylene group and again where necessary dsomerisation of an ethylenic bond at the 5(10)- or 5,6-position to the ,5- position or of a 17 -acetyl side chain to a 17a~acetyl side chain., 5· A process according to Claim k in which the compound of formula III is a 3-enol ether, 3~enol-acylate, 3-enol-thioether, 3-ej.amine, 3-ketal, 3-thioketal, or 3- hemithioketal of a , - or 5(10)- ethylenic-3-ketone<> 6. A process according to Claim 5 in which the compound of formula III is a 3-alkoxy-2,5(l0)-diene<, X-50-fa A process according to Claim substantially as described herein and shown with reference to any one of Examples 80 A process according to Claim k substantially as described herein and shown with reference to any one of Examples 5 to » o A process according to Claim k substantially as described herein and shown with reference to any one of Examples 10 to 12« 10ο· A process according to Claim substantially as described herein and shown with reference to Example 13 or Example lk„ of the several formula given in Glain 1 llo A steroid compound/produced by a process according to any one of Claims to 100 17-acetyl-13/¾-ethyl-gon-4-en-3-one 12o A pharmaceutical composition comprising a j6 e»oid-eeapowa4 according to any one of Claims 1 to 3 an 11 in association with a pharmaceutically acceptable carriedo Dated this 18th day of December, 1966